Thursday, 1 August 2013

UK Rituximab Trial

My interest
in ME/CFS was sparked when I was invited, unexpectedly, by IiME to the IiMEC8 Conference in May.

The meeting
was impressive: not just professional science, but at a high level. I was
particularly impressed that negative findings were given adequate weight.

It became
clear to me that there was a community committed to identifying and encouraging
the very best research in a difficult and neglected field.

I was aware
of the study by Fluge and Mella, using rituximab. I had not been surprised to
see some patients respond, but the type of response, which was similar to what
we had found in rheumatoid arthritis fifteen years ago, caught my attention. In
fact, the situation seemed very reminiscent of the time when we first started
to get results with targeted therapy in rheumatoid arthritis. We had the
benefit of more immunological clues then, but on the other hand, the experience
we have gained over the last decade now makes things easier in other ways.

My limited
understanding of ME/CFS is that, like arthritis, it is probably several
diseases with similar symptoms. Most colleagues who specialise in ME/CFS seem
to agree. What the Fluge/Mella study suggests is that perhaps half of those
suffering from these symptoms may have a B cell-dependent autoimmune disease.

A recent
study by Dr Amolak Bansal and colleagues also suggests that B cells may be
functioning abnormally in a significant proportion of people with ME/CFS.

To me, a key
feature of this approach, unlike chasing one particular virus or gene, is that,
if confirmed, it will provide a broad base for understanding disease
mechanisms.

Even if
rituximab is a cumbersome treatment in the short term its use may not only help
a good proportion of patients directly but also begin to show us how to divide
ME/CFS into different groups. So it may be useful even for those whose disease
does not respond because once separated out from B cell-dependent disease the
role of other factors such as NK cell function or cerebral blood flow may
become clear.

Looking at
the research directions currently being pursued in ME/CFS, I am in no doubt
that the usage of rituximab is one of the most promising. There is clearly
enthusiasm for further trials. However, rituximab is not an easy drug to use
and many doctors do not feel confident with using it. This may explain why
studies have been slow to gain momentum outside Norway.

Safe and
effective usage requires understanding of B cell life history and function.
Each condition has to be considered differently, especially in terms of when
treatment is repeated. But with experience its use is very effective and
probably as safe as most drugs.

After the
IiME Conference I began thinking about my personal experience of patients and
friends with ME/CFS. I was sent a copy of ‘Lost Voices ‘ by IiME, which made me
think more. It struck me that, whether or not results are positive, further
trials of rituximab for ME/CFS should be encouraged not only because impact on
life for those affected can be so severe but also because further trials could
give clues to disease mechanism. I am retired and would not be personally
involved but have suggested to IiME that I would be happy to advise and to
encourage others to set up a trial.

My feeling
is that a trial should be carried out somewhere with detailed experience in use
of rituximab in autoimmune conditions.

The UCL
service set up when we started treating rheumatoid arthritis, lupus and a range
of other conditions has the most extensive experience.

There is
laboratory expertise in B cell immunology under Dr Jo Cambridge.

UCL also has
a new Clinical Trials Research Facility with staff appointed to manage trials
of this sort.

Importantly,
there is enthusiasm amongst local teams for a rituximab ME/CFS trial.

I have
suggested to IiME that this would be the ideal centre for such a trial, to be
set up in collaboration with clinicians with expertise in ME/CFS from around
London, and in particular Dr Bansal.

IiME have
accepted this and this is the planned and preferred research base for this
trial.

Clinical
trials are costly. The trial planned in Norway to confirm the results from
Fluge and Mella’s initial trial will cost something like £1-2M pounds. I think
it would be most sensible to set up a smaller scale trial initially in the UK
with a focus on trying to identify which patients are most likely to benefit. A
trial treating about 30 patients, giving useful scientific information should
hopefully be feasible for around £3-400,000. Trial design will require careful
thought and some further preliminary laboratory work is likely to be needed
before it is clear what design would be optimal.

Nevertheless,
I am optimistic that a trial could be set up without major delay if funds can
be raised. If the role of B cells in at least some ME/CFS, suggested by Fluge
and Mella’s study, can be confirmed I think there is a genuine chance of
getting to grips with the mechanism of the disease.

From there
on things can only get easier.

Statement from Invest in ME:

The
statement above from Professor Edwards is an astonishing opportunity for those
patients with ME and their families.

To have
somebody of Professor Edwards' standing produce such a statement, after
agreeing to advise the charity following the IIMEC8 conference, justifies
completely the conference theme of Mainstreaming ME Research.

This is a
potential breakthrough for state-of-the-art biomedical research into ME.

We believe
this study would add great value to other similar research being performed
elsewhere.

It would
also put the UK into the forefront of ME research.

There is no
greater expert able to advise on a trial of rituximab than Professor Edwards
who formally established the validity of B cell depletion in autoimmune
disorders via his groundbreaking rituximab trials.

At the Biomedical Researchinto ME Collaborative meeting (BRMEC) organised by Invest in ME and the
Alison Hunter Memorial Foundation Dr Jo Cambridge from UCL was invited by the
charity to attend and present to the 40 researchers from nine countries
gathered in London for the meeting. We felt it important to get the best advice
possible to help with this area of ME research. Dr Cambridge added an enormous
amount to the meeting – followed by a sincere and positive approach to
progressing research.

UCL, as
Professor Edwards has explained, has first-class facilities and we believe this
opportunity is unique in the UK.

If the UK patient community wish to have a
rituximab study then this is as good as it gets.

With the
clinical team and Dr Cambridge at UCL performing this work, and with Professor
Edwards as advisor, we are sure that a huge leap in understanding ME will be
possible.

IiME have
managed to work with the experts to set up this possibility. As Professor
Edwards states “a trial could be set up without major delay if funds can be
raised”.

Our
fundraising campaign now must begin in earnest.

We invite
everyone to get behind this UK rituximab study and support us.

We welcome
contributions from other organisations and companies and individuals. The
quality of the researchers and the facilities is beyond doubt.

IiME will
contact other organisations to invite them to donate to this cause. One
organisation has already indicated it will support a rituximab trial – in fact
the MEA chairman has publicly stated on 29th July to an IiME supporter - “Let
us know when you find some good quality researchers with a peer reviewed
proposal. We have £60,000 in a ring fenced pot awaiting such a development.”.

We now have
the researchers willing to perform this trial in the UK.

The quality
of the researchers and the facilities at their disposal place the capability of
the UCL team to perform this trial beyond doubt.

What Next?

There is
enthusiasm for setting up a study at UCL.

UCL can take
this forward in collaboration with Dr Bansal and with close liaison, including
visits, with Bergen. This has been agreed.

A meeting
has been arranged for Professor Edwards to visit Bergen to discuss with Dr Fluge.

Further
trips by the UCL team would be a possibility and will be arranged by the
charity.

We welcome
this as this will undoubtedly help both the Norwegian and the UK studies.

We need to
raise funding for this study so we urge all our supporters, and others who wish
to have a UK rituximab trial or wish to advance biomedical research into ME, to
raise awareness and interest from as many sources as possible and support us in
this venture.

This UK
rituximab study has been initiated by IiME and the UCL staff who were at our
conference and BRMEC research meeting.

The best
research team possible to undertake this trial is able to perform this.

About Me

I am a Christian, saved by grace alone through faith alone. I have had the neuroimmune disorder ME, Myalgic Encephalomyelitis, since 1991. From North Somerset, now in N. Ireland. Please see my website for further information about ME.